Fluoxetine

Abstract

Fluoxetine is a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). Although its mechanism of action in anxiety disorders is unclear, it is thought to act by enhancing serotonergic neurotransmission and down-regulating central receptors. In comparison with other SSRIs, fluoxetine has a long elimination half-life (4 days). Fluoxetine (usual dosage =20 mg/day) for ≥8 weeks was as effective as citalopram, desipramine, imipramine and moclobemide in double-blind trials involving patients with panic disorder; extension studies demonstrated sustained efficacy for up to 12 months. Fluoxetine 20 to 60 mg/day was also significantly better than placebo in the treatment of obsessive-compulsive disorder; response rates were 24 to 54% after 8 to 13 weeks of treatment compared with 7 and 26% for placebo. However, some response rates were significantly lower with fluoxetine than with clomipramine in some studies, although fluvoxamine and sertraline were of similar efficacy to fluoxetine according to a meta-analysis. Sustained or continued improvement was seen with fluoxetine treatment for up to 1 year. Fluoxetine 10 to 80 mg/day for ≥4 weeks significantly improved symptoms of post-traumatic stress disorder from baseline values and, in social anxiety disorder, improved symptoms in the majority of patients studied. Double-blind studies indicate that fluoxetine is as effective in patients with anxiety symptoms and depression as imipramine, clomipramine and amitriptyline. Preliminary data indicate that fluoxetine, sertraline and paroxetine are similarly effective in patients with depression and high baseline anxiety. However, more research is needed in this area. Fluoxetine is well tolerated, with similar incidences of adverse events to that seen with sertraline. However, fluoxetine is associated with fewer adverse effects than fluvoxamine and paroxetine. Rates of sexual dysfunction and suicidal ideation with fluoxetine appear similar to those seen with other SSRIs. Withdrawal reactions after discontinuation of medication are less common with fluoxetine than with other SSRIs. Conclusion: Fluoxetine is effective in the short term treatment of panic, social anxiety, post-traumatic stress and obsessive-compulsive disorders, and may be effective in patients experiencing anxiety symptoms and depression. Continued or sustained improvements for up to 1 year have been seen in patients with panic or obsessive-compulsive disorder. More research is needed to determine the comparative clinical efficacy of fluoxetine with regard to other SSRIs and clomipramine, and its efficacy in long term treatment. Fluoxetine is well tolerated, with fewer withdrawal reactions than other SSRIs, and is a useful option in first-line therapy for most anxiety disorders.